Inhalation atomizer comprising a blocking function and a counter

ABSTRACT

The invention is directed to an inhalation atomizer comprising a counter and a blocking function. Counter rotates each time the atomizer is actuated. The blocking function includes a first protrusion on the counter and a second protrusion on a lower unit of the atomizer. Once the predetermined number of actuations has been achieved, the first protrusion encounters the second protrusion and prevents further rotation of the counter so that the atomizer is blocked from further use.

This application claims the benefit of priority to U.S. ProvisionalPatent Application Ser. No. 62/494,875 filed on Aug. 24, 2016, thedisclosure of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The current invention refers to an inhalation atomizer comprising ablock function through a locking mechanism and a counter. After apredetermined number of actuations, the atomizer can be properly blockedby the locking mechanism. The inhalation atomizer has a substitutableand insertable container, a nozzle system and a pressure generator alongwith a drive spring. The number of actuations of the device can becounted by a mechanical counter.

BACKGROUND OF THE INVENTION

WO-93/21980 discloses a metered-dose inhaler, wherein the inhalationdose of a drug substance is introduced by means of a hand-operateddevice, from a supply of the drug substance contained in the inhaler,into a chamber from which the dose is expelled with the current of airwhich the user sucks in through the inhaler as they breathe in. Themetered-dose inhaler is fitted with a counter which comprises arotatable screw spindle and a rod, one end of which engages in the formof a nose in the thread of the screw spindle. The rod moves parallel tothe screw spindle as the rotation of the spindle increases. The counterindicates, by means of the position of the nose-like end of the rod, thenumber of doses which have already been taken out of the supply of drugsubstance, or those which can still be taken out. The other end of therod is movably held in a guide shaft into which the rod extends moredeeply as the rotation of the screw spindle increases. As soon as thesupply of the drug substance in the inhaler is coming to an end, thenose-like end of the rod engaging in the screw spindle reaches that partof the spindle which has a number of courses of thread having a greaterpitch than the rest of the screw spindle. As a result, on each rotationof the screw spindle, the rod moves along faster than before. The otherend of the rod meanwhile bears on a flexible lever, and furtheractuation of the metered-dose inhaler is prevented.

WO-97/20590 discloses a locking stressing mechanism for aspring-actuated output drive. WO-97/24586 discloses a mechanical counterfor a metering device. WO-97/12687 describes a device for generatinghigh pressure in a fluid in a miniature arrangement provided with alocking stressing mechanism and a counter. The apparatus is used toatomize a fluid to produce an inhalable aerosol. WO-01/64268 describes aneedleless injector which contains a locking stressing mechanism.

The components of device equipment described above are intended forrepeated use, e.g. for repeated atomization of a given amount of liquidto produce an aerosol for inhalation into the lungs, or for needlelessinjection of a given quantity of liquid underneath the skin of humans oranimals. The quantity of liquid atomized or injected may contain atherapeutically active sub stance.

U.S. Pat. No. 7,396,341 discloses a blocking device for an inhalationapparatus which comprises a locking-stressing-mechanism with anoperating spring and a spring transfer member in which is accommodated apiston which is mounted to be moveable in a cylinder, and thesecomponents are housed in a two part housing which comprises an upperhousing part and a lower housing part, said upper housing part having aninner wall and said lower housing part having an outer wall, and the twoparts are mounted to be rotatable relative to each other, and saidoperating spring is tensioned by means of a screw thrust gear bymanually rotating said two housing parts relative to each other, and atthe same time as said housing parts are rotated relative to each other amechanical counter is actuated which comprises a threaded spindle and aslider, and said threaded spindle is mounted in said wall of the lowerhousing part, and said slider is moved along said spindle by an amountwhich depends on the number of rotations of said two housing partsrelative to each other, wherein a recess is provided in said outer wallof said lower housing part and in said inner wall of said upper housingpart, and the two recesses are opposite each other when said two housingparts are in a given rotary position, and a moveable blocking element isprovided which is located initially only in the recess in said lowerhousing part and a push rod for moving said blocking element partiallyinto the recess in said upper housing part to prevent the upper andlower housing parts from rotating relative to each other is providedwhich cooperates with said slider on said spindle of said counter.

An inhalation atomizer comprising a new blocking function through alocking mechanism and a new counter is presented in this invention,which has significant advantages over the prior arts and is able tolimit the period of use of the inhalation atomizer so that safetyrequirements are meet. The limitation may be beneficial in terms oftechnical, medical or hygiene considerations.

After a predetermined number of actuations, the inhalation atomizer inthe current invention will be appropriately blocked through a lockingmechanism. The locking mechanism is realized mainly by two protrusions.Protrusion A is located on the outer wall of the lower unit of theinside part. Protrusion B is located on the inner wall of counter. Whenthe atomizer is actuated each time, the counter will make a rotationwith a constant angle around the lower unit of the inside part. Once thepredetermined number of actuations is achieved, Protrusion A andProtrusion B will encounter with each other and hence the counter willbe prevented from further rotation. Therefore the atomizer is blockedand stopped from further use. The number of actuations of the device canbe counted by the counter.

SUMMARY OF THE INVENTION

The current invention is directed to an inhalation atomizer device orapparatus comprising a block function and a counter which will reliably,effectively and finally prevent further use of the apparatus after agiven number of actuations if there is a compelling reason for this.After a predetermined number of actuations, the atomizer will beappropriately blocked through a locking mechanism. The locking mechanismis realized mainly by two protrusions. Protrusion A is located on theouter wall of the lower unit of the inside part. Protrusion B is locatedon the inner wall of counter. The lower unit of the inside part isnested in the counter. The counter can rotate relative to the lower unitof the inside part. Because of the rotation of the counter, the numberdisplayed on the counter can change as the actuation number increases,and can be observed by the patient. After each actuation, the numberdisplayed on the counter has a change. Once the predetermined number ofactuations is achieved, Protrusion A and Protrusion B will encounterwith each other and hence the counter will be prevented from furtherrotation. Therefore the atomizer is blocked and stopped from furtheruse. The number of actuations of the device can be counted by thecounter.

According to a first embodiment, the current invention is directed to aninhalation atomizer comprising a block function through lockingmechanism. The locking function is realized according to the inventionby an inhalation atomizer device having the following characterizingfeatures:

-   -   Protrusion A is provided on the outer wall of the lower unit of        the inside part and Protrusion B is provided on the inner wall        of the counter. Two protrusions are on the same horizontal        level.    -   A continuous indentation is provided on the counter so that the        Protrusion B on the outer wall of the lower unit of the inside        part can move rotatably in the indentation. Therefore the        relative rotation between the counter and the lower unit of the        inside part is feasible. After certain angles of rotation, the        two protrusions will encounter with each other and hence further        rotation will be prevented.

According to a second embodiment, the current invention is directed to acounter with a continuous indentation. A protrusion on the counter canbe installed on the inner wall of the counter. In this embodiment of thecurrent invention, the continuous indentation of the counter should beinstalled on the inner wall of the counter, and the two protrusionsshould be on the same horizontal level so that the relative rotationbetween the counter and the lower unit of the inside part is feasible.During the normal use of the atomizer, the protrusion of the lower unitof the inside part can move rotatably in the continuous indentation ofthe counter.

In preferred embodiment of the current invention, the protrusion of thecounter can be installed on the top of the counter. In this situation,there is no need to have the continuous indentation on the counter.Instead the protrusion of the lower unit should be on the samehorizontal level with the protrusion of the counter. During the normaluse of the atomizer, the protrusion of the lower unit move rotatably atthe top of the counter.

In a preferred embodiment of the current invention, the blockingelements may be protrusions on the wall of the counter and lower unit,preferably made by plastic materials.

The blocking function through the locking mechanism according to thecurrent invention has the following advantages:

-   -   It is appropriate for miniaturized apparatus.    -   It is easy to assemble.    -   The protrusions are located on the inner wall of the counter and        on the outer wall of the lower unit of the inside part. When the        atomizer is used, the patient cannot access the protrusions        because of their positions.    -   The predetermined number of actuations can be modified based on        the positions of the counter when it is assembled. Therefore        re-opening and injecting new mold is not required to adjust the        predetermined number of actuations and hence the cost is saved.    -   Once the predetermined number of actuations is achieved,        Protrusion A and Protrusion B will encounter with each other and        hence the counter will be prevented from further rotation.        Therefore the atomizer is blocked and stopped from further use.

The blocking function according to the current invention is used forexample in a high pressure atomizer or in a needleless injector. Amedical liquid administered using such a device may contain a drugdissolved in a solvent. Suitable solvents include, for example, water,ethanol or mixture thereof.

The third aspect of the current invention is further directed to aninhalation atomizer comprising the block function and the counterdescribed above. The inhalation atomizer is preferably a portable andhand-held device for delivering the pharmaceutical formulation ormedicaments to the patients through a soft mist inhalation. In apreferred embodiment of the current invention, when such inhalationatomizer is stressed or an intended dose delivery every time, apre-determined amount of fluid is preferably released automatically.

In a preferred embodiment of the current invention, a precursory amountof fluid to be expelled before every actual dose to rinsing the nozzleis not required for the inhalation atomizer of the current invention.The inhalation atomizer comprising the locking function and the counterof the current invention can provide adequate fluids to deliver the fulldose of the pre-determined dose numbers, even after allowing theinhalation atomizer to rinse the device system at least 5 times byexpelling the full dose amount of the fluids before the actual dose tothe patients. The dose numbers can alternatively be countered by asensor or an electronic digital counter attached or integrated with theinhalation atomizer of the current invention.

DESCRIPTION OF THE INVENTIONS

According to a first embodiment, the current invention is directed to aninhalation atomizer device or apparatus which will reliably, effectivelyand finally prevent further use of the apparatus after a given number ofactuations if there is a compelling reason for this. After apredetermined number of actuations, the atomizer will be appropriatelyblocked through a locking mechanism. The locking mechanism is realizedmainly by two protrusions. Protrusion A is located on the outer wall ofthe lower unit of the inside part. Protrusion B is located on the innerwall of counter. The lower unit of the inside part is nested in thecounter. The counter can rotate relative to the lower unit of the insidepart. Because of the rotation of the counter, the number displayed onthe counter can change as the actuation number increases, and can beobserved by the patient. After each actuation, the number displayed onthe counter has a change. Once the predetermined number of actuations isachieved, Protrusion A and Protrusion B will encounter with each otherand hence the counter will be prevented from further rotation. Thereforethe atomizer is blocked and stopped from further use. The number ofactuations of the device can be counted by the counter.

According to a second embodiment, the current invention is directed toan inhalation atomizer with a block function through locking mechanism.The locking function is realized according to the invention by aninhalation atomizer device having the following characterizing features:

-   -   Protrusion A is provided on the outer wall of the lower unit of        the inside part and Protrusion B is provided on the inner wall        of the counter. Two protrusions are on the same horizontal        level.    -   A continuous indentation is provided on the counter so that the        Protrusion B on the outer wall of the lower unit of the inside        part can move rotatably in the indentation. Therefore the        relative rotation between the counter and the lower unit of the        inside part is feasible. After certain angles of rotation, the        two protrusions will encounter with each other and hence further        rotation will be prevented.

The blocking function through the locking mechanism according to thecurrent invention has the following advantages:

-   -   It is appropriate for miniaturized apparatus.    -   It is easy to assemble.    -   The protrusions are located on the inner wall of the counter and        on the outer wall of the lower unit of the inside part. When the        atomizer is used, the patient cannot access the protrusions        because of their positions.    -   The predetermined number of actuations can be modified based on        the positions of the counter when it is assembled. Therefore        re-opening and injecting new mold is not required to adjust the        predetermined number of actuations and hence the cost is saved.    -   Once the predetermined number of actuations is achieved,        Protrusion A and Protrusion B will encounter with each other and        hence the counter will be prevented from further rotation.        Therefore the atomizer is blocked and stopped from further use.

The blocking function according to the current invention is used forexample in a high pressure atomizer or in a needleless injector. Amedical liquid administered using such a device may contain a drugdissolved in a solvent. Suitable solvents include, for example, water,ethanol or mixture thereof.

FIGS. 1 and 2 demonstrate a preferred embodiment of the blockingfunction according to the current invention. These two figures showpartial longitudinal sections through the wall of the lower unit 17 band the counter 26. The longitudinal sections run parallel to the axisof the lower unit 17 b and the counter 26.

In FIG. 1, the atomizer is in the un-locking state. The lower unit 17 bof the inside part 17 is nested in the counter 26. The relative rotationbetween the lower unit 17 b and the counter 26 is feasible. On the innerof the counter 26, there is a continuous indentation 27 and a protrusionB 29 (which is not showed in the FIG. 1). There is also a protrusion A28 on the outer of the lower unit 17 b, which is on the same horizontallevel with the protrusion B 29 and can move rotatably in the continuousindentation 27. When the atomizer is actuated each time, the counter 26will make a rotation with a constant angle around the lower unit 17 b.As the actuation number is increasingly close to the predeterminednumber of actuations, the protrusions A and B are getting closer andcloser. Until when the predetermined number of actuations is reached,the protrusions A and B encounter with each other, namely the lockingstate showed in the FIG. 2. Therefore the counter will be prevented fromfurther rotation and hence the atomizer is locked and stopped fromfurther use.

According to a second embodiment, the current invention is directed to acounter with a continuous indentation. A protrusion on the counter canbe installed on the inner wall of the counter. In this embodiment of thecurrent invention, the continuous indentation of the counter should beinstalled on the inner wall of the counter, and the two protrusionsshould be on the same horizontal level so that the relative rotationbetween the counter and the lower unit of the inside part is feasible.During the normal use of the atomizer, the protrusion of the lower unitof the inside part can rotate around in the continuous indentation ofthe counter.

In preferred embodiment of the current invention, the protrusion of thecounter can be installed on the top of the counter. In this situation,there is no need to have the continuous indentation on the counter.Instead the protrusion of the lower unit should be on the samehorizontal level with the protrusion of the counter. During the normaluse of the atomizer, the protrusion of the lower unit can rotate aroundat the top of the counter.

The atomizer 1 preferably includes a counter element showed in FIG. 5.The counter element has a worm 24 and a counter ring 26. The counterring 26 is preferred circular and has dentate part at the bottom. Theworm 24 has upper and lower end gears. The upper end gear contacts withthe upper shell 16. The upper shell 16 has inside bulge 25. When theatomizer 1 is employed, the upper shell 16 rotates; and when the bulge25 passes through the upper end gear of the worm 24, the worm 24 isdriven to rotate. The rotation of the worm 24 drives the rotation of thecounter ring 26 through the lower end gear. Then it results in thecounting effect.

The third aspect of the current invention is further directed to aninhalation atomizer device as well as a procedure and/or an operation ofthe inhalation atomizer comprising the blocking function and the counterdescribed above. Through easy and simple steps and operations of thisinhalation device, an accurate metering of the inhalation aerosol couldbe achieved.

The third aspect of the current invention is further directed to aninhalation atomizer comprising the block function and the counterdescribed above. The inhalation atomizer is preferably a portable andhand-held device for delivering the pharmaceutical formulations ormedicaments to the patients through a soft mist inhalation. In apreferred embodiment of the current invention, a precursory amount offluid to be expelled before every actual dose to rinsing the nozzle isnot necessary for the inhalation atomizer of the current invention. Thelocking function and the counter in the current invention can provideadequate or enough fluids to deliver the pre-determined doses, evenafter allowing the inhalation atomizer to rinse the device system atleast 3 times by expelling the full dose amount of the fluids before theactual dose. The dose numbers can alternatively be countered or trackedby a touch sensor or an electronic digital counter attached orintegrated with the atomizer of the current invention.

A typical example of the inhalation atomizer 1 comprising the blockfunction and the counter described above of the current invention isshown in FIG. 3, FIG. 4 and FIG. 6. The current invention of theatomizer 1 comprising the block function and the counter described aboveincludes, but not limited to, the inhalation device provided in FIG. 3,FIG. 4 and FIG. 6. The current invention of the atomizer 1 comprisingthe block function and the counter described above further comprises theinhalation atomizer device which can be modified from these presented inFIG. 3, FIG. 4 and FIG. 6. FIG. 6 shows the picture of the devicefeatures inside the inhalation atomizer 1 from the 3D drawing.

A typical example of the inhalation atomizer 1 comprising the blockfunction and the counter described above for spraying a medicament fluid2 is demonstrated in the FIG. 3 as non-stressed state and in the FIG. 4as stressed state. The atomizer 1 comprising the block function and thecounter described above is preferred as a portable inhaler and requiresno propellant gas.

For the typical atomizer 1 comprising the block function and the counterdescribed above, an aerosol 14 that can be inhaled by a patient isgenerated through the atomization of the fluid 2, which is preferredformulated as a medicament liquid. The medicament is typicallyadministered at least once a day, more specifically multiple times aday, preferred at predestined time gaps, according to how serious theillness affects the patient.

A preferred atomizer 1 comprising the block function and the counterdescribed above has substitutable and insertable vessel 3, whichcontains the medicament fluid 2. Therefore, a reservoir for holding thefluid 2 is formed in the vessel 3. Specifically, the medicament fluid 2is located in the fluid compartment 4 formed by a collapsible bag in thevessel 3.

A preferred adequate amount of fluid 2 for the inhalation atomizer 1comprising the block function and the counter described above is in thevessel 3 to provide, i.e., up to 200 doses. A classical vessel 3 has avolume of 2 to 10 ml. A pressure generator 5 in the atomizer 1 is usedto deliver and atomize the fluid 2, specifically in a predestined dosageamount. Therefore, the fluid 2 could be released and sprayed inindividual doses, specifically from 5 to 30 microliter.

The typical atomizer 1 comprising block function and the counterdescribed above may preferably have a pressure generator 5 and a holder6, a drive spring 7, and a locking part 8 which is preferred manuallyoperated to discharge it, a delivering tube 9, a non-return valve 10, apressure room 11, and a nozzle 12 in the area of a mouthpiece 13. Thevessel 3 is latched by the holder 6 in the atomizer 1 so that thedelivering tube 9 is plunged into the vessel 3. The vessel 3 could beseparated from the atomizer 1 for substitution.

For the atomizer 1 comprising block function and the counter describedabove, when drive spring 7 is stressed in axial direction, thedelivering tube 9, the vessel 3 along with the holder 6 will be shifteddownwards. Then the fluid 2 will be sucked into the pressure room 11through delivering tube 9 and the non-return valve 10.

For the inhalation atomizer 1 comprising the block function and thecounter described above, after the locking part 8 is actuated to releasethe holder 6, then the stress is eased. During this process, thedelivering tube 9 and closed non-return valve 10 are shifted back upwardby releasing the drive spring 7. Consequently, the fluid 2 is under thepressure in the pressure room 11. Then the fluid 2 is pushed through thenozzle 12 and atomized into an aerosol 14 by the pressure. A patientcould inhale the aerosol 14 through the mouthpiece 13, while the air issucked into the mouthpiece 13 through air inlets 15.

The inhalation atomizer 1 comprising the block function and the counterdescribed above has an upper shell 16. Then an inside part 17, whichcould be rotated relative to the upper shell 16, has an upper unit 17 aand a lower unit 17 b. A lower shell 18 is manually operable to attachonto the inside part 17 preferred through the holding unit 19. The lowershell 18 could be separated from the atomizer 1 so that the vessel 3could be substituted and inserted.

The inhalation atomizer 1 comprising the block function and the counterdescribed above may preferably have the lower shell 18, which carriesthe inside part 17, is rotatable relative to the upper shell 16. As aresult of rotation and engagement between the upper unit 17 a and theholder 6, through a gear 20, the holder 6 is axially moved the counterto the force of the drive spring 7 and the drive spring 7 is stressed.

In the typical stressing state, the vessel 3 is shifted downwards andreaches to a final position, which is demonstrated in the FIG. 4. Thedrive spring 7 is stressed under this final position. Then the holder 6is clasped by the locking part 8. Therefore, the vessel 3 and thedelivering tube 9 are prevented from moving upwards so that the drivespring 7 is stopped from easing.

The typical atomizing process occurs after the locking part 8 releasesthe holder 6. The vessel 3, the delivering tube 9 and the holder 6 areshifted back by the drive spring 7 to the beginning position in the FIG.3. This is described as major shifting in here. While the major shiftingoccurs, the non-return valve 10 is closed and the fluid 2 is under thepressure in the pressure room 11 by the delivering tube 9, and then thefluid 2 is pushed out and atomized by the pressure.

The inhalation atomizer 1 comprising the block function and the counterdescribed above may preferably have a clamping function. During theclamping, the vessel 3 preferably performs a lifting shift or for thewithdrawal of the fluid 2 during the atomizing process. The gear 20 hassliding surfaces 21 and 22 on the upper shell 16 and/or on the holder 6,which could make holder 6 axially move when the holder 6 is rotatedrelative to the upper shell 16.

In this clamping function, when the holder 6 is in the clamping position(FIG. 4), the sliding surfaces 21 and 22 move out of engagement. Thenthe gear 20 releases the holder 6 for the opposite shift axially.Meanwhile, the locking part 8 changes into locking position so that thedelivering tube 9, the vessel 3 and the holder 6 are in the stressingstate. In particular the locking part 8 is of annular construction andin its locking position is radically shifted out of the normallyconcentric arrangement with the holder 6 so that the holder 6 abuts withits end face on a portion of the locking part 8 and is blocked thereby.

The inhalation atomizer 1 comprising the block function and the counterdescribed above may preferably have the locking part 8 which may beactuated by a button 23 to shift back to its concentric position so thatthe atomizing process is activated. The holder 6 may be not blocked fortoo long and can carry on the major shifting. Therefore, the fluid 2 ispushed out and atomized.

Nevertheless, the drug formulation solution presented in the currentinvention may also be applied to other atomizers or inhalers, includingpowder inhalers, metered dose inhalers and so forth.

The atomizer 1 comprising the block function and the counter describedabove is specifically devised to spray medicament aerosol 14 as aninhaler. Still, it can also be devised for cosmetic use with theadjustment on the content in the vessel 3, specifically as a perfumeatomizer.

The fluid 2 is preferably a liquid, specifically an aqueous medicine orethanolic medicine formulation. Nevertheless, it may also be applied forother types of formulation such as suspensions or powders.

According to the current invention the preferred pharmaceutical activeingredients and/or formulations of the preferred fluid 2 are listedbelow. The pharmaceutical active ingredients may be formulated asaqueous or non-aqueous solutions, mixtures, ethanol-containing orsolvent-free formulations.

In preferred aspect of the current invention, the fluid 2 used in theinhalation atomizer device comprising the block function and the counterdescribed above comprises the compounds as single pharmaceuticalingredient active or in combination of two or more pharmaceuticalingredient actives. The pharmacologically active substance is preferablyselected from among the betamimetics, anticholinergics, corticosteroids,PDE4-inhibitors, LTD4-antagonists, EGFR-inhibitors, dopamine agonists,H1-antihistamines, PAF4-antagonists and PI3-kinase inhibitors. Moreover,double or triple combinations of W may be combined and used in thedevice according to the invention. Combinations of the pharmaceuticalactive ingredient might be, for example:

A betamimetic, combined with an anticholinergic, corticosteroid,PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,

An anticholinergic, combined with a betamimetic, corticosteroid,PDE4-inhibitor, EGFR-inhibitor 60 or LTD4-antagonist,

A corticosteroid, combined with a PDE4-inhibitor, EGFR-inhibitor orLTD4-antagonist,

A PDE4-inhibitor, combined with an EGFR-inhibitor or LTD4-antagonist

An EGFR-inhibitor, combined with an LTD4-antagonist.

In a more specifically preferred aspect of the current invention, thecompounds and their pharmaceutically acceptable salts used asbetamimetics the fluid 2 used in the inhalation atomizer devicecomprising the block function and the counter described above arepreferably selected from among vilanterol, olodaterol, indacaterol,albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol,clenbuterol, fenotrol, formoterol, metaprotereol, hexoprenaline,ibuterol, isoetharine, isoprenaline, levosalbutamol, mabuterol,meluadrine, metaproterenol, orciprenaline, pirbuterol, procaterol,reproterol, rimiterol, ritodrine, salmefamol, salmeterol, soterenol,sulphonterol, terbutaline, tiaramide, tolubuterol, zinterol, CHF-1035,HOKU-81, KUL-1248 and

-   3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzyl-sulphonamide,-   5-[2-(5,6-diethylindan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one,-   4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulphonyl}ethyl]-amino}ethyl]-2(3H)-benzothiazolone,-   1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol,-   1-[3-(4-methoxybenzyl-amino)-4-hydroxyphenyl]-2-[4-(1-benzimidazolyl)-2-methyl-2-butyl    amino]ethanol,-   1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-N,N-dimethylaminophenyl)-2-methyl-2-propylamino]ethanol,-   1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propyl    amino]ethanol,-   1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-n-butyloxyphenyl)-2-methyl-2-propylamino]ethanol,-   1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-{4-[3-(4-methoxyphenyl)-1,2,4-triazol-3-yl]-2-methyl-2-butylaminoethanol,-   5-hydroxy-8-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one,-   1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butylamino)ethanol,-   6-hydroxy-8-{1-hydroxy-2-[2-(4-methoxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo    [1,4] oxazin-3-one,-   6-hydroxy-8-{1-hydroxy-2-[2-(ethyl-4-phenoxy-acetate)-1,1-dimethyl-ethylamino]-ethyl}-4    H-benzo[1,4]oxazin-3-one,-   6-hydroxy-8-{1-hydroxy-2-[2-(4-phenoxy-acetic    acid)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one,-   8-{2-[1,1-dimethyl-2-(2,4,6-trimethylphenyl)-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo    [1, 4]oxazin-3-one,-   6-hydroxy-8-{1-hydroxy-2-[2-(4-hydroxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo[1,4]    oxazin-3-one,-   6-hydroxy-8-{1-hydroxy-2-[2-(4-isopropyl-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-4H-benzo-   [1,4] oxazin-3-one-   8-{2-[2-(4-ethyl-phenyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one,-   8-{2-[2-(4-ethoxy-pheyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo    [1,4]oxazin-3-one,-   4-(4-{2-[2-hydroxy-2-(6-hydroxy-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-ethylamino]-2-methyl-propyl}-phenoxy)-butyric    acid,-   8-{2-[2-(3,4-difluoro-phenyl)-1,1-dimethyl-ethylamino]-1-hydroxy-ethyl}-6-hydroxy-4H-benzo    [1,4] oxazin-3-one,-   1-(4-ethoxy-carbonylamino-3-cyano-5-fluorophenyl)-2-(tert-butylamino)ethanol,-   2-hydroxy-5-(1-hydroxy-2-{2-[4-(2-hydroxy-2-phenyl-ethylamino)-phenyl]-ethylamino}-ethyl)-benzaldehyde,-   N-[2-hydroxy-5-(1-hydroxy-2-{2-[4-(2-hydroxy-2-phenyl-ethylamino)-phenyl]-ethylamino}-ethyl)-phenyl]-formamide,-   8-hydroxy-5-(1-hydroxy-2-{2-[4-(6-methoxy-biphenyl-3-ylamino)-phenyl]-ethylamino}-ethyl)-1    H-quinolin-2-one,-   8-hydroxy-5-[1-hydroxy-2-(6-phenethylamino-hexy-lamino)-ethyl]-1H-quinolin-2-one,-   5-[2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one,-   [3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-5-methyl-phenyl]-urea,-   4-(2-{6-[2-(2,6-dichloro-benzyloxy)-ethoxy]-hexylamino}-1-hydroxy-ethyl)-2-hydroxymethyl-phenol,-   3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyloxy}-butyl)-benzylsulphonamide,-   3-(3-{7-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-heptyloxy}-propyl)-benzylsulphonamide,-   4-(2-{6-[4-(3-cyclopentanesulphonyl-phenyl)-butoxy]-hexylamino}-1-hydroxy-ethyl)-2-hydroxymethyl-phenol,-   N-adamantan-2-yl-2-(3-{2-[2-hydroxy-2-(4-hydroxy-3-hy-droxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetamide,    optionally in the form of the racemates, enantiomers, diastereomers    thereof and optionally in the form of the pharmacologically    acceptable acid addition salts, solvates or hydrates thereof.    According to the invention the acid addition salts of the    betamimetics are preferably selected from among the hydrochloride,    hydrobromide, hydroiodide, hydrosulphate, hydrophosphate,    hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate,    hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate,    hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

In a more specifically preferred aspect of the current invention, theanticholinergics used in the fluid 2 of the inhalation atomizer devicecomprising the block function and the counter described above arepreferably selected from among aclidinium salts, preferably the bromidesalt, umeclidinium salts, preferably the bromide salt, the tiotropiumsalts, preferably the bromide salt, oxitropium salts, preferably thebromide salt, flutropium salts, preferably the bromide salt, ipratropiumsalts, preferably the bromide salt, glycopyrronium salts, preferably thebromide salt, trospium salts, preferably the chloride salt, tolterodine.In the above-mentioned salts the cations are the pharmacologicallyactive constituents. As anions the above-mentioned salts may preferablycontain the chloride, bromide, iodide, sulphate, phosphate,methanesulphonate, nitrate, maleate, acetate, citrate, fumarate,tartrate, oxalate, succinate, benzoate or p-toluenesulphonate, whilechloride, bromide, iodide, sulphate, methanesulphonate orp-toluenesulphonate are preferred as counter-ions. Of all the salts thechlorides, bromides, iodides and methanesulphonates are particularlypreferred.

Other preferred anticholinergics are selected from among the salts offormula AC-1

wherein X— denotes an anion with a single negative charge, preferably ananion selected from among the fluoride, chloride, bromide, iodide,sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate,citrate, fumarate, tartrate, oxalate, succinate, benzoate andp-toluenesulphonate, preferably an anion with a single negative charge,particularly preferably an anion selected from among the fluoride,chloride, bromide, methanesulphonate and p-toluenesulphonate,particularly preferably bromide, optionally in the form of theracemates, enantiomers or hydrates thereof. Of particular importance arethose pharmaceutical combinations which contain the enantiomers offormula AC-1-en

wherein X— may have the above-mentioned meanings. Other preferredanticholinergics are selected from the salts of formula AC-2

wherein R denotes either methyl or ethyl and wherein X— may have theabove-mentioned meanings. In an alternative embodiment the compound offormula AC-2 may also be present in the form of the free base AC-2-base.

In another preferred aspect of the current invention, specifiedcompounds are selected from tropenol 2,2-diphenylpropionatemethobromide, scopine 2,2-diphenylpropionate methobromide, scopine2-fluoro-2,2-diphenylacetate methobromide, tropenol2-fluoro-2,2-diphenylacetate methobromide; tropenol3,3,4,4,-tetrafluorobenzilate methobromide, scopine3,3′4,4′-tetrafluorobenzilate methobromide; tropenol4,4′-difluorobenzilate methobromide, scopine 4,4′-difluorobenzilatemethobromide, tropenol 3,3′-difluorobenzilate methobromide, scopine3,3,-difluorobenzilate methobromide, tropenol9-hydroxy-fluorene-9-carboxylate methobromide, tropenol9-fluoro-fluorene-9-carboxylate methobromide, scopine9-hydroxy-fluorene-9-carboxylate methobromide, scopine9-fluoro-fluorene-9-carboxylate methobromide, tropenol9-methyl-fluorene-9-carboxylate methobromide, scopine9-methyl-fluorene-9-carboxylate methobromide, cyclopropyltropinebenzilate methobromide, cyclopropyltropine 2,2-diphenylpropionatemethobromide, cyclopropyltropine 9-hydroxy-xanthene-9-carboxylatemethobromide, cyclopropyltropine methyl 4,4′-difluorobenzilatemethobromide, tropenol 9-hydroxy-xanthene-9-carboxylate methobromide,scopine 9-hydroxy-xanthene-9-carboxylatemethobromide, tropenol9-methyl-xanthene-9-carboxylate methobromide, scopine9-methyl-xanthene-9-carboxylate methobromide, tropenol,9-ethyl-xanthene-9-carboxylatemethobromide, tropenol9-difluoromethyl-xanthene-9-carboxylatemethobromide. The above-mentionedcompounds may also be used as salts within the scope of the presentinvention.

In a more preferred aspect of the current invention, the corticosteroidsused in the fluid 2 of the inhalation atomizer device comprising theblock function and the counter described above are selected from amongbeclomethasone, betamethasone, budesonide, butixocort, ciclesonide,deflazacort, dexamethasone, etiprednol, flunisolide, fluticasone,loteprednol, mometasone, prednisolone, prednisone, rofleponide,triamcinolone, RPR-106541, NS-126,(S)-fluoromethyl-6,9-difluoro-17-[(2-furanylcarbonyl)oxy]-11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionate,optionally in the form of the racemates, enantiomers or diastereomersthereof and optionally in the form of the salts and derivatives thereof,the solvates and/or hydrates thereof. Any reference to steroids includesa reference to any salts or derivatives, hydrates or solvates thereofwhich may exist. Examples of possible salts and derivatives of thesteroids may be: alkali metal salts, such as for example sodium orpotassium salts, sulphobenzoates, phosphates, isonicotinates, acetates,dichloroacetates, propionates, dihydrogen phosphates, palmitates,pivalates or furoates.

In a more specifically preferred aspect of the current invention, thecorticosteroids used in the fluid 2 of the inhalation atomizer devicecomprising the block function and the counter described above areselected from fluticasone propionate and fluticasone furoate.

PDE4-inhibitors used in the fluid 2 of the inhalation atomizer devicecomprising the block function and the counter described above arepreferably selected from compounds among enprofyllin, theophyllin,roflumilast, ariflo (cilomilast), tofimilast, pumafentrin, lirimilast,60 arofyllin, atizoram, D-4418, Bay-198004, BY343, CP-325.366, D-4396(Sch-351591), AWD-12-281 (GW-842470), NCS-613, CDP-840, D-4418,PD-168787, T-440, T-2585, V-11294A, C1-1018, CDC-801, CDC-3052, D-22888,YM-58997, Z-15370 andN-(3,5-dichloro-1-oxo-pyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide(−)p-[(4aR*,10bS*)-9-ethoxy-1,2,3,4,4a,10b-hexahydro-8-methoxy-2-methylbenzo[s][1,6]naphthyridin-6-yl]-N,N-diisopropylbenzamide,(R)-(+)-1-(4-bromobenzyl)-4-[(3-cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone3-(cyclopentyloxy-4-methoxyphenyl)-1-(4-N,-[N-2-cyano-S-methyl-isothioureido]benzyl)-2-pyrrolidone,cis[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylicacid]2-carbomethoxy-4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)cyclohexan-1-one,cis[4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethox-yphenyl)cyclohexan-1-ol](R)-(+)-ethyl[4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate(S)-(−)-ethyl[4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-ylidene]acetate9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-thienyl)-9H-pyrzolo[3,4-c]-1,2,4-triazolo [4,3-a]pyridine,9-cyclopentyl-5,6-dihydro-7-ethyl-3-(tert-butyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo [4,3-a]pyridine, optionally in the form of theracemates, enantiomers or diastereomers thereof and optionally in theform of the pharmacologically acceptable acid addition salts thereof,the solvates and/or hydrates thereof. According to the invention theacid addition salts of the betamimetics are preferably selected fromamong the hydrochloride, hydrobromide, hydroiodide, hydrosulphate,hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate,hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate,hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

The LTD4-antagonists used in the fluid 2 of the inhalation atomizerdevice comprising the block function and the counter described above arepreferably selected from compounds of zileuton, montelukast, pranlukast,zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507, (LM-1507), VUF-5078,VUF-K-8707, L-733321 and1-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethenyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)thio)methylcyclopropane-acetic acid,1-(((1R)-3-3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetic acid, [2-[[2-(4-tert-butyl-2-thiazolyl)-5-benzofuranyl]oxymethyl]phenyl acetic acid, optionally in the form of the racemates, enantiomersor diastereomers thereof and optionally in the form of thepharmacologically acceptable acid addition salts, solvates and/orhydrates thereof. According to the invention the acid addition salts ofthe betamimetics are preferably selected from among the hydrochloride,hydrobromide, hydroiodide, hydro sulphate, hydrophosphate,hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate,hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate,hydrobenzoate and hydro-p-toluenesulphonate. By salts or derivativeswhich the LTD4-antagonists may optionally be capable of forming aremeant, for example: alkali metal salts, such as for example sodium orpotassium salts, alkaline earth metal salts, sulphobenzoates,phosphates, isonicotinates, acetates, propionates, dihydrogenphosphates, palmitates, pivalates or furoates.

EGFR-inhibitors used in the fluid 2 of the inhalation atomizer devicecomprising the block function and the counter described above arepreferably selected from compounds of selected from among necitumumab,cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]-amino}-7-cyclopropyl methoxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-diethylamino)-1-oxo-2-buten-1-1]amino}-7-cyclopropyl-methoxy-quinazoline4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-cyclopropyl-methoxy-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopentyloxy-quinazoline,4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cy-clopropylmethoxy-quinazoline,4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline,4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-((R)-2-meth-oxymethyl-6-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline,4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-((S)-6-methyl-2-oxo-morpholin-4-yl)-ethoxy]-7-methoxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl)amino}-7-cyclopropylmethoxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethy-lamino)-1-oxo-2-buten-1-yl]amino}-7-cyclopentyloxy-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-{[4-(N,N-to-(2-methoxy-ethyl)-amino)-1-oxo-2-buten-1-yl]amino}-7-cyclopropy-lmethoxy-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-ethyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(tetrahydropyran-4-yl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethy-lamino)-1-oxo-2-buten-1-yl]amino}-7-((R)-tetrahydrofuran-3-yloxy)-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethy-lamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopentyloxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N-cyclopropyl-N-methyl-amino)-1-oxo-2-buten-1-yl]amino}-7-cyclo-pentyloxy-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethy-lamino)-1-oxo-2-buten-1-yl]amino}-7-[(R)-(tetrahydrofuran-2-yl)methoxy]-quinazoline,4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethy-lamino)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-2-yl)methoxy]-quinazoline,4-[(3-ethynyl-phenyl)amino]-6,7-to-(2-methoxy-ethoxy)-quinazoline-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)-4propyloxy]-6-[(vinyl-carbonyl)amino]-quinazoline,4-[(R)-(1-phenyl-ethyl)amino]-6-(4-hydroxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine3-cyano-4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-ethoxy-quinoline,ro-4-fluorophenyl)amino]-6-(1-cyan-piperidin-4-yloxy)-7-methoxy-quinazolineoptionally in the form of the racemates, enantiomers, diastereomersthereof and optionally in the form of the pharmacologically acceptableacid addition salts, solvates or hydrates thereof.

According to the invention the acid addition salts of the betamimeticsused in the fluid 2 of the inhalation atomizer device comprising theblock function and the counter described above are preferably selectedfrom among the hydrochloride, hydrobromide, hydroiodide, hydrosulphate,hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate,hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate,hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

The dopamine agonists used in the fluid 2 of the inhalation atomizerdevice comprising the block function and the counter described above arepreferably selected from compounds among bromocriptin, cabergoline,alpha-dihy-droergocryptine, lisuride, pergolide, pramipexol, roxindol,ropinirol, talipexol, tergurid and viozan, optionally in the form of theracemates, enantiomers, diastereomers thereof and optionally in the formof the pharmacologically acceptable acid addition salts, solvates orhydrates thereof. According to the invention the acid addition salts ofthe betamimetics are preferably selected from among the hydrochloride,hydro-bromide, hydroiodide, hydrosulphate, hydrophosphate,hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate,hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate,hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

H1-Antihistamines used in the fluid 2 of the inhalation atomizer devicecomprising the block function and the counter described above arepreferably selected from compounds among desloratadine, olopatadine,azelastine, epinastine, cetirizine, azelas-tine, fexofenadine,levocabastine, loratadine, mizolastine, ketotifen, emedastine,dimetindene, clemastine, bamipine, cexchlorpheniramine, pheniramine,doxylamine, chlorophenoxamine, dimenhydrinate, diphenhydramine,promethazine, ebastine, desloratidine and meclozine, optionally in theform of the racemates, enantiomers, diastereomers thereof and optionallyin the form of the pharmacologically acceptable acid addition salts,solvates or hydrates thereof. According to the invention the acidaddition salts of the betamimetics are preferably selected from amongthe hydrochloride, hydro-bromide, hydroiodide, hydrosulphate,hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate,hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate,hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

In addition, the compound used in the fluid 2 of the inhalation atomizerdevice comprising the block function and the counter described above arepreferably selected from the groups of ergot alkaloid derivatives, thetriptans, the CGRP-inhibitors, the phosphodiesterase-V inhibitors,interleukin-5 antagonists, kinase inhibitors, anti-PD-1, endothelinreceptor antagonists, antibiotics, surfactants, anti-IgE, mast cellstabilizers, anti-RSV, CFTR-relevant compounds, IPF treatments, sGCstimulators, vasodilators, Alpha-Proteinase Inhibitors, antiarrhythmic,enzymes, sclerosing agents optionally in the form of the racemates,enantiomers or diastereomers thereof, optionally in the form of thepharmacologically acceptable acid addition salts, the solvates and/orhydrates thereof.

Examples of ergot alkaloid derivatives are dihydroergotamine andergotamine.

Examples of interleukin-5 antagonists are reslizumab and mepolizumab.

Examples of kinase inhibitors are alectinib, osimertinib, nintedanib,ceritinib, crizotinib and gefitinib.

Examples of anti-PD-1 are pembrolizumab and nivolumab.

Examples of endothelin receptor antagonists are macitentan, ambrisentanand bosentan.

Examples of antibiotics are telavancin, bedaquiline, aztreonam,ceftaroline, tigecycline, telithromycin, moxifloxacin, clarithromycin,ceftibuten, piperacillin, tazobactam, amoxicillin/clavulanate,sparfloxacin, grepafloxacin, cefdinir, ciprofloxacin, cefuroxime,dirithromycin, Gatifloxacin, ertapenem, Cefazolin, rifapentine andtobramycin.

Examples of surfactants are lucinactant, calfactant and poractant alpha.

Example of phosphodiesterase-V inhibitors is tadalafil.

Example of anti-IgE is omalizumab.

Examples of mast cell stabilizers are nedocromil and cromolyn.

Example of anti-RSV is palivizumab.

Examples of CFTR-relevant compounds are lumacaftor and ivacaftor.

Example of IPF-treatments is pirfenidone.

Example of sGC stimulators is riociguat.

Example of vasodilators is treprostinil.

Examples of antiarrhythmic are dofetilide and verapamil.

Examples of enzymes are dornase alfa and laronidase.

Example of sclerosing agents is sterile talc.

Preferably, the current invention provides an inhalation atomizer devicecomprising a locking function and a counter described above which canaccommodate the liquid pharmaceutical compositions for multiple doses ina container or cartridge, wherein the fluid 2 pharmaceutical compositioncomprises aclidinium bromide, formoterol fumarate, indacaterol maleate,glycopyrrolate bromide, fluticasone furoate, vilanterol trifenatate,umeclininium bromide, tiotropium bromide, olodaterol hydrochloride,ipratropium bromide or albuterol sulfate, including any theirpharmaceutically acceptable salts, or any their combination as theactive ingredient(s).

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function and a counter described above whichcan accommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of aclidinium bromide andformoterol fumarate or any their pharmaceutically acceptable salts asthe active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a lock function and a counter described above whichcan accommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of indacaterol maleate andglycopyrrolate bromide or any their pharmaceutically acceptable salts asthe active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function described above which canaccommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of fluticasone furoate andvilanterol trifenatate or any their pharmaceutically acceptable salts asthe active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function described above which canaccommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of vilanterol trifenatate andumeclininium bromide or any their pharmaceutically acceptable salts asthe active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function described above which canaccommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a triple combination of fluticasone furoate,vilanterol trifenatate and umeclininium bromide or any theirpharmaceutically acceptable salts as the active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function described above which canaccommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of tiotropium bromide andolodaterol hydrochloride or any their pharmaceutically acceptable saltsas the active ingredients.

More preferably, the current invention provides an inhalation atomizerdevice comprising a locking function described above which canaccommodate the liquid pharmaceutical compositions for multiple unitdoses in a container or cartridge, wherein the pharmaceuticalcomposition comprising a combination of ipratropium bromide andalbuterol sulfate or any their pharmaceutically acceptable salts as theactive ingredients.

The term “pharmaceutically acceptable” means that which is useful inpreparing a pharmaceutical composition that is generally non-toxic andis not biologically undesirable and includes that which is acceptablefor veterinary use and/or human pharmaceutical use.

The term “pharmaceutical composition” or “pharmaceutical formulation” isintended to encompass a drug product including the active ingredient(s),pharmaceutically acceptable excipients that make up the carrier, as wellas any product which results, directly or indirectly, from combination,complexation or aggregation of any two or more of the ingredients.Accordingly, the pharmaceutical compositions of the present inventionencompass any composition made by admixing the active ingredient, activeingredient dispersion or composite, additional active ingredient(s), andpharmaceutically acceptable excipients.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: A Schematic View of the Blocking Function in Non-locking State

FIG. 2: A Schematic View of the Blocking Function in Locking State

FIG. 3: A Schematic View of the Atomizer in Non-Stressed State

FIG. 4: A Schematic View of the Atomizer in Stressed State AfterRotation Through 90 Degree as Related to FIG. 1

FIG. 5: A Schematic View of Counter Element of the Atomizer

FIG. 6: A Schematic View of the Atomizer from 3D Drawing

LIST OF REFERENCE NUMERALS

-   1: Atomizer-   2: Fluid-   3: Vessel-   4: Fluid Compartment-   5: Pressure Generator-   6: Holder-   7: Drive spring-   8: Locking part-   9: Delivering tube-   10: Non-return valve-   11: Pressure room-   12: Nozzle-   13: Mouthpiece-   14: Aerosol-   15: Air Inlet-   16: Upper Shell-   17: Inside Part-   17 a: Upper Unit-   17 b: Lower Unit-   18: Lower Shell-   19: Holding Unit-   20: Gear-   21: Sliding Surface-   22: Sliding Surface-   23: Button-   24: Worm-   25: Bulge-   26: Counter-   27: Continuous Indentation-   28: Protrusion A-   29: Protrusion B-   H major shifting-   S stressing shifting

I claim:
 1. An inhalation atomizer comprising: (a) a counter comprisinga worm, a counter ring, and an upper shell, wherein the counter ring iscircular with a bottom having an indentation, the worm has an upper endgear and a lower end gear, which contact the upper shell, and the uppershell comprises an inside bulge, and when the bulge passes through theupper end gear of the worm, the worm is driven to rotate, which drivesrotation of the counter ring through the lower end gear, resulting in acounting effect; (b) a blocking function comprising a locking mechanismwhich comprises a lower unit, wherein a lower unit comprises (i) a firstprotrusion which is nested in the indentation of the counter ring and(ii) a second protrusion, wherein the first protrusion and secondprotrusion are on the same horizontal level and able to move and rotatein the indentation, such that when the inhalation atomizer is actuated,the counter ring rotates around the lower unit with a constant angle,and when the first and second protrusions encounter each other, thecounter is prevented from further rotation, locking the atomizer andstopping it from further use; (c) a fluid in a vessel; (d) a nozzle forthe delivery and atomization of the fluid, wherein the fluid isdelivered in metered individual full-doses; and (e) a delivering elementin the form of a delivering tube, which is movable for delivering andatomizing the fluid.
 2. The inhalation atomizer according to claim 1,wherein the fluid contains a solvent.
 3. The atomizer according to claim1, wherein the fluid comprises a pharmaceutical active ingredientselected from the group consisting of anticholinergics, betamimetics,steroids, phosphodiesterase IV-inhibitors, LTD4-antagonists andEGFR-kinase-inhibitors, antiallergics, ergot alkaloid derivatives,triptans, CGRP-antagonists, phosphodiesterase-V-inhibitors, and anycombination of the foregoing.
 4. The inhalation atomizer according toclaim 1, wherein the fluid comprises a pharmaceutical active ingredientselected from the group consisting of aclidinium bromide, formoterolfumarate, indacaterol maleate, glycopyrrolate bromide, fluticasonefuroate, vilanterol trifenatate, umeclidinium bromide, tiotropiumbromide, olodaterol hydrochloride, ipratropium bromide, albuterolsulfate, any pharmaceutically acceptable salts thereof, and anycombination thereof.
 5. The inhalation atomizer according to claim 1,wherein the fluid comprises a pharmaceutical active ingredient selectedfrom the group consisting of a combination of aclidinium bromide andformoterol fumarate.
 6. The inhalation atomizer according to claim 1,wherein the fluid comprises a pharmaceutical active ingredient selectedfrom the group consisting of a combination of indacaterol maleate andglycopyrrolate bromide, and any pharmaceutically acceptable saltsthereof.
 7. The inhalation atomizer according to claim 1, wherein thefluid comprises a pharmaceutical active ingredient selected from thegroup consisting of a combination of fluticasone furoate and vilanteroltrifenatate.
 8. The inhalation atomizer according to claim 1, whereinthe fluid comprises a pharmaceutical active ingredient selected from thegroup consisting of a combination of fluticasone furoate, vilanteroltrifenatate and umeclidinium bromide, and any pharmaceuticallyacceptable salts thereof.
 9. The inhalation atomizer according to claim1, wherein the fluid comprises a pharmaceutical active ingredientselected from the group consisting of tiotropium bromide and anypharmaceutically acceptable salts thereof.
 10. The inhalation atomizeraccording to claim 1, wherein the fluid comprises a pharmaceuticalactive ingredient selected from the group consisting of a combination oftiotropium bromide and olodaterol hydrochloride, and anypharmaceutically acceptable salts thereof.
 11. The inhalation atomizeraccording to claim 1, wherein the fluid comprises a pharmaceuticalactive ingredient selected from the group consisting of olodaterolhydrochloride and any pharmaceutically acceptable salts thereof.
 12. Theinhalation atomizer according to claim 1, wherein the fluid comprises apharmaceutical active ingredient selected from the group consisting of acombination of ipratropium bromide and albuterol sulfate, and anypharmaceutically acceptable salts thereof.
 13. A method for inhalationdelivery of an atomized fluid in individual, metered full-doses througha nozzle, comprising atomizing a fluid with the inhalation atomizer ofclaim
 1. 14. A blocking function comprising a locking mechanism and acounter, wherein: (a) the counter comprises a worm and a counter ring,wherein the counter ring is circular having a bottom with a continuousindentation, the worm has an upper end gear and a lower end gear thatcontact an upper shell, and the upper shell comprises an inside bulge,such that when the bulge passes through the upper end gear of the worm,the worm is driven to rotate, which drives rotation of the counter ringthrough the lower end gear, resulting in a counting effect; and (b) theblocking function comprises a lower unit, which comprises (i) a firstprotrusion which is nested in the continuous indentation of the counterring and (ii) a second protrusion, wherein the first protrusion andsecond protrusion are on the same horizontal level and able to move androtate in the continuous indentation, such that when the inhalationatomizer is actuated, the counter ring rotates around the lower unitwith a constant angle, and when the first and second protrusionsencounter each other, the counter is prevented from further rotation,locking the atomizer and stopping it from further use.